Abstract

MicroRNAs (miRNAs) are the non-coding RNAs that can both attach to the untranslated and coding sections of target mRNAs, triggering destruction or post-transcriptional alteration. miRNAs regulate various cellular processes such as immune function, apoptosis, and tumorigenesis. About 35,000 miRNAs have been discovered in the human genome. The increasing evidence suggests that the dysregulation of human miRNAs may have a role in the etiology of some disorders including cancer. Only a small sub-set of human miRNAs has functionally been validated in the pathogenesis of oncogenic viruses such as Kaposi’s sarcoma-associated herpesvirus (KSHV). KSHV is the cause of various human malignancies including primary effusion lymphoma (PEL) and Kaposi’s sarcoma (KS), which are mainly seen in AIDS patients or other immunocompromised people. We aimed to identify the miRNAs in Kaposi’s sarcoma cases, with the comparison of KSHV seropositive and seronegative tumors with the controls and in each other in Turkish Kaposi’s sarcoma patients. We performed the miRNA-sequencing at genome level in the peripheral blood mononuclear cells of 16 Kaposi’s sarcoma patients, and in 8 healthy controls matched for age, gender, and ethnicity. A total of 642 miRNA molecules with different expression profiles were identified between the patients and the healthy controls. Currently, out of 642 miRNAs, 7 miRNAs (miR-92b-3p, miR-490-3p, miR-615-3p, miR-629-5p, miR-1908, miR-3180, miR-4433b-3p) which have not been described in the literature in the context of Kaposi’s sarcoma were addressed in the study for the first time and 9 novel miRNAs, not found previously in the database, have been detected in Kaposi’s sarcoma using the miRNA-sequencing technique. This study demonstrates the identification of differently expressed miRNAs which might be the new therapeutic targets for Kaposi’s sarcoma, that has limited treatment options and can be used in the etiology, diagnosis, and prognosis of this cancer.

Highlights

  • MicroRNAs are the single-stranded small (19–25 nucleotides long) non-coding RNA molecules, which play a role in various biological processes [1, 2]. miRNAs regulate the target gene silencing by binding to complementary sequences of mRNA in the 3′-untranslated regions [3, 4] and participate in cell death, proliferation, differentiation, and signal transduction [5]

  • The peripheral blood mononuclear cells of 16 Kaposi’s sarcoma patients, who presented to our clinic between 2017 and 2019, and of 8 healthy individuals matched for age, sex, and ethnicity with the patients and with no history of cancer in the family for 3 generations were investigated in the study

  • We performed the genome level miRNA-sequencing in the peripheral blood mononuclear cells of 16 Turkish Kaposi’s sarcoma patients that are HIV negative and 8 healthy controls, who were matched in terms of age, gender, and ethnicity with the patients

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Summary

Introduction

MicroRNAs (miRNAs) are the single-stranded small (19–25 nucleotides long) non-coding RNA molecules, which play a role in various biological processes [1, 2]. miRNAs regulate the target gene silencing by binding to complementary sequences of mRNA in the 3′-untranslated regions [3, 4] and participate in cell death, proliferation, differentiation, and signal transduction [5]. Oncogenic/tumor suppressor miRNAs, as well as those involved in proliferation, angiogenesis, and other cellular processes, play an essential role in cancer [6] and miRNAs can be used as diagnostic and therapeutic response indicators. Kaposi’s sarcoma is a type of cancer that develops from the lining cells of blood or lymph vessels. The tumors (lesions) usually occur on the skin, may commonly manifest in the mouth, gastrointestinal system, and respiratory tract. Kaposi’s sarcoma is a rare type of cancer but endemic to Southern, and Eastern Africa. The disease was the most frequent cause of cancer incidence and mortality among men in Mozambique and Uganda in 2020. The highest number of Kaposi’s Sarcoma patients were detected in men in Mozambique, and women in Zambia [10]

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